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(MMP-9) protects the adult brain after cerebral ischemia. However, the role of MMP-9 in the immature brain after hypoxia-ischemia (HI) is unknown. We exposed MMP-9 (Ϫ/Ϫ) [MMP-9 knock-out (KO)] and wild-type (WT) mice to HI on postnatal day 9. HI was induced by unilateral ligation of the left carotid artery followed by hypoxia (10% O 2 ; 36°C). Gelatin zymography showed that MMP-9 activity was transiently increased at 24 h after HI in the ipsilateral hemisphere and MMP-9-positive cells were colocalized with activated microglia. Seven days after 50 min of HI, cerebral tissue volume loss was reduced in MMP-9 KO (21.8 Ϯ 1.7 mm 3 ; n ϭ 22) compared with WT (32.3 Ϯ 2.1 mm 3 ; n ϭ 22; p Ͻ 0.001) pups, and loss of white-matter components was reduced in MMP-9 KO compared with WT pups (neurofilament: WT, 50.9 Ϯ 5.4%; KO, 18.4 Ϯ 3.1%; p Ͻ 0.0001; myelin basic protein: WT, 57.5 Ϯ 5.8%; KO, 23.2 Ϯ 3.5%; p ϭ 0.0001). The neuropathological changes were associated with a delayed and diminished leakage of the blood-brain barrier (BBB) and a decrease in inflammation in MMP-9-deficient animals. In contrast, the neuroprotective effects after HI in MMP-9-deficient animals were not linked to either caspase-dependent (caspase-3 and cytochrome c) or caspase-independent (apoptosis-inducing factor) processes. This study demonstrates that excessive activation of MMP-9 is deleterious to the immature brain, which is associated with the degree of BBB leakage and inflammation. In contrast, apoptosis does not appear to be a major contributing factor.","publication_date":"2007,,","publication_name":"Journal of Neuroscience","grobid_abstract_attachment_id":"43674386"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Matrix Metalloproteinase-9 Gene Knock-out Protects the Immature Brain after Cerebral Hypoxia-Ischemia","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [33981879,34156939]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 'edu.academia.applesignon';</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div 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blood–brain barrier disruption after photothrombotic cerebral ischemia in rats</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32636054" href="https://independent.academia.edu/StevenGoldman1">Steven Goldman</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Acta Neurochirurgica, 2009</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Early activation of matrix metalloproteinase-9 is associated with blood–brain barrier disruption after photothrombotic cerebral ischemia in rats","attachmentId":86624092,"attachmentType":"pdf","work_url":"https://www.academia.edu/80144000/Early_activation_of_matrix_metalloproteinase_9_is_associated_with_blood_brain_barrier_disruption_after_photothrombotic_cerebral_ischemia_in_rats","alternativeTracking":true}"><span 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href="https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice">Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="66014727" href="https://independent.academia.edu/SarahGeorge40">Sarah George</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neurobiology of Disease, 2004</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice","attachmentId":53714994,"attachmentType":"pdf","work_url":"https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="28271669" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/28271669/Proteolytic_activity_during_cortical_development_is_distinct_from_that_involved_in_hypoxic_ischemic_injury">Proteolytic activity during cortical development is distinct from that involved in hypoxic ischemic injury</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="52995281" href="https://independent.academia.edu/ArjanScheepens">Arjan Scheepens</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuroscience, 2009</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Proteolytic activity during cortical development is distinct from that involved in hypoxic ischemic injury","attachmentId":48596768,"attachmentType":"pdf","work_url":"https://www.academia.edu/28271669/Proteolytic_activity_during_cortical_development_is_distinct_from_that_involved_in_hypoxic_ischemic_injury","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/28271669/Proteolytic_activity_during_cortical_development_is_distinct_from_that_involved_in_hypoxic_ischemic_injury"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="104769122" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter">Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39378877" href="https://independent.academia.edu/HidekazuTomimoto">Hidekazu Tomimoto</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Cerebral Blood Flow &amp; Metabolism, 2001</p><p class="ds-related-work--abstract ds2-5-body-sm">White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2–expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood–brain barrier. These findings suggest tha...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter","attachmentId":104409592,"attachmentType":"pdf","work_url":"https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":43674386,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":43674386,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_43674386" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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href="https://independent.academia.edu/MarHernandezGuillamon">Mar Hernández-Guillamon</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Cerebral Blood Flow &amp; Metabolism, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinase-13 is Activated and is found in the Nucleus of Neural Cells after Cerebral Ischemia","attachmentId":92793472,"attachmentType":"pdf","work_url":"https://www.academia.edu/88896522/Matrix_Metalloproteinase_13_is_Activated_and_is_found_in_the_Nucleus_of_Neural_Cells_after_Cerebral_Ischemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38634677" href="https://independent.academia.edu/CarolinaMaier">Carolina Maier</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke; a journal of cerebral circulation, 2004</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix metalloproteinase-9 and myeloperoxidase expression: quantitative analysis by antigen immunohistochemistry in a model of transient focal cerebral ischemia","attachmentId":40147655,"attachmentType":"pdf","work_url":"https://www.academia.edu/18594797/Matrix_metalloproteinase_9_and_myeloperoxidase_expression_quantitative_analysis_by_antigen_immunohistochemistry_in_a_model_of_transient_focal_cerebral_ischemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" 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reperfusion injury is associated to MMP2 and IL-1β elevation in cortical neurons of rats subjected to middle cerebral artery occlusion</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="46811561" href="https://bham.academia.edu/MichelangeloCerto">Dr Michelangelo Certo</a></div><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Early reperfusion injury is associated to MMP2 and IL-1β elevation in cortical neurons of rats subjected to middle cerebral artery occlusion","attachmentId":47024544,"attachmentType":"pdf","work_url":"https://www.academia.edu/26745078/Early_reperfusion_injury_is_associated_to_MMP2_and_IL_1%CE%B2_elevation_in_cortical_neurons_of_rats_subjected_to_middle_cerebral_artery_occlusion","alternativeTracking":true}"><span 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decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in rats</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="118582829" href="https://tzuchi.academia.edu/%E5%AE%97%E9%B7%B9%E9%99%B3">宗鷹陳</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Pineal Research, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in 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js-related-work-sidebar-card" data-collection-position="13" data-entity-id="94717053" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/94717053/Astrocytic_Induction_of_Matrix_Metalloproteinase_9_and_Edema_in_Brain_Hemorrhage">Astrocytic Induction of Matrix Metalloproteinase-9 and Edema in Brain Hemorrhage</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="46354116" href="https://independent.academia.edu/EmiriMandeville">Emiri Mandeville</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Cerebral Blood Flow &amp; Metabolism, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Astrocytic Induction of Matrix Metalloproteinase-9 and Edema in 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href="https://www.academia.edu/17884064/Neuronal_self_injury_mediated_by_IL_1%CE%B2_and_MMP_9_in_a_cerebral_palsy_model_of_severe_neonatal_encephalopathy_induced_by_immune_activation_plus_hypoxia_ischemia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="16" data-entity-id="13674419" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/13674419/Matrix_metalloproteinase_2_plays_a_critical_role_in_the_pathogenesis_of_white_matter_lesions_after_chronic_cerebral_hypoperfusion_in_rodents">Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents</a><div class="ds-related-work--metadata"><a 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